ADHD medication review and discontinuation - Australian ADHD Clinical Practice Guideline

5. Pharmacological interventions

5.5 Medication Review and Discontinuation

Clinical Questions

Are there specific clinical effects of discontinuing from pharmacological treatment and if so, how should these be supported?

Clinical practice gaps, uncertainties and need for guidance

There are inconsistencies in practice with respect to the consideration and management of medication discontinuation. The effects of withdrawing treatment need to be considered for the person with ADHD and their families and carers. ADHD is a lifelong condition and treatment is likely to be beneficial and needed throughout one’s life. In some individual circumstances or during particular periods, consideration of discontinuation may be necessary.

Children and adolescents
Adults

Evidence for stopping methylphenidate vs. continuing methylphenidate
An evidence review was completed with new evidence found in one study. A single RCT, with low risk of bias and moderate certainty for all outcomes, was conducted in children and adolescents (aged 8–18 years) with ADHD over 7 weeks (Matthijssen et al., 2019, 2020). The study compared discontinuation (defined as gradual withdrawal of extended-release methylphenidate to placebo over a 3-week period, followed by 4 weeks of complete placebo), with continued active medication (extended-release methylphenidate).

There was statistically significant harm of discontinuation based on the investigator-rated Clinical Global Impression scale in terms of the number of participants with worsened ADHD symptoms; however, there were no statistically significant differences for ADHD total, inattention, and hyperactive symptoms, and for other symptoms (ADHD index, cognitive/ inattention and hyperactivity) based on clinician and teacher report.

NICE identified clinically important harm of withdrawal for ADHD for total symptoms (self-rated; one study of moderate quality and parent-rated; one study of moderate quality) and for Clinical Global Impression scale (one study of moderate quality) at 2 weeks.

Evidence for stopping methylphenidate vs. continuing methylphenidate in participants who may not have all experienced a positive response to methylphenidate
No new evidence was found. There was clinically important harm of withdrawal for the following outcomes at 4 weeks: ADHD inattention/overactivity symptoms – parent-rated (one study of low quality) and teacher-rated (one study of low quality); other symptoms – parent-rated (one study of low quality) and teacher-rated (one study of low quality); and Clinical Global Impression (one study of low quality).

Evidence for stopping atomoxetine vs. continuing atomoxetine
No new evidence was found. There was a clinically important benefit of withdrawal for adverse events (one study of low quality). Clinically important harms of withdrawal were seen on the following outcome measures: ADHD symptoms total among children who had been receiving treatment for 3 months (investigator-rated; one study of moderate quality); ADHD symptoms total among children who had been receiving treatment for 12 months (investigator-rated; one study of moderate quality); relapse at 9 months among children receiving treatment for 3 months (one study of moderate quality); and relapse at 6 months among children receiving treatment for 12 months (one study of low quality).

Evidence for stopping lisdexamfetamine vs continuing lisdexamfetamine
No new evidence was found. There were no clinically important benefits of withdrawal for other outcomes (parent-rated; one study of low quality) at 6 weeks. There was clinically important harm of withdrawal for ADHD symptoms (investigator-rated; one study of very low quality) at 6 weeks.

Evidence for stopping methylphenidate vs. continuing methylphenidate
No new evidence was found. There was a clinically important benefit of withdrawal for adverse outcomes post-treatment (self-rated one study of low quality). There were no clinically important benefits of withdrawal for quality of life (one study of very low quality), ADHD total symptoms (self-rated; one study low quality) or other symptoms (one study very low quality) at 4 weeks. There was clinically important harm of withdrawal for ADHD symptoms total on those who relapsed at 4 weeks (2 studies of very low quality) and at 6 months (one study moderate quality).

Evidence for stopping Atomoxetine vs. continuing Atomoxetine
No new evidence was found. There was a clinically important benefit of withdrawal for adverse events (one study low quality) after 25 weeks. There were no clinically important benefits of withdrawal at >25 weeks for quality of life (one study of high quality), ADHD total symptoms (self-rated; one study of moderate quality and carer-rated; one study of moderate quality), and self-harm (one study of low quality).

Evidence for stopping lisdexamfetamine vs continuing lisdexamfetamine
No new evidence was found. There was clinically important harm of withdrawal at >4 weeks for ADHD total symptoms (one study of moderate quality) and Clinical Global Impression scale (one study of very low quality).

Evidence to recommendation statement

Evidence identified concerns around lack of follow‑up and the opportunity to review medication choices and this was supported by the experience of the GDG. The GDG agreed that a yearly review with an ADHD specialist should be a comprehensive assessment that revisits the areas discussed when starting treatment and also the effect of current treatment. This would ensure that decisions around continuing or stopping treatment are fully informed.

Limited evidence showed possible worsening of ADHD symptoms on stopping medication but supported a reduction in adverse effects after withdrawal. The GDG used their experience to make a recommendation on emphasising the importance of assessing the overall benefits and harms of medication as part of a review. The GDG agreed that it was important to highlight the elements of a medication review that are important for someone with ADHD; they based the elements on evidence on adverse effects of medication, adherence and information and support.

Recommendations

Clinical considerations for implementation of the recommendations

These recommendations will likely reinforce current best practice. Clinicians should ensure they also follow local prescribing laws regarding review and renewal permits for stimulant medication. Consideration of discontinuation should be addressed with the person with ADHD or their caregivers at least annually and can be incorporated into ongoing care, in line with other relevant recommendations (see section 5.1 and section 5.3). The recommendations made here are generally well established in clinical practice, and are therefore likely to be acceptable to stakeholders.

See Technical Report, section 10.5 for further details